The hypothesis of seasonality of twin births was investigated in two important maternity hospitals in the State of Sāo Paulo, Brazil. The study included 1,386 twin births that occurred among 154,699 deliveries from 1984 to 1993. No evidence of seasonality has been detected either for the twin birth rate considered as a whole or for dizygotic twinning rate. The distributions of these rates fitted well sinusoidal regression curves but the cyclic trend did not correspond to any specific season.

Several lines of evidence have accumulated in recent years indicating that nuclear cytoplasmic interactions play an important role in the formation and fate of the developing mouse embryo. Early nuclear transplantation experiments indicated that the ability of nuclei to direct cleavage after transfer into enucleated zygotes falls abruptly with nuclei from more advanced preimplantation stages [1]. Transcriptional activation of the nuclei, which occurs during the second cell cycle probably precludes the reprogramming of nuclei from later cleavage stages [2]. Thus, when an 8-cell nucleus is transferred to an enucleated zygote, such a reconstituted zygote is blocked at the 2-cell stage. However, when identical 8-cell nuclei were transferred into both blastomeres of enucleated 2-cell embryos, they were able to support development to the blastocyst stage and even gave rise to live offspring [2-4]. This indicated the importance of the cytoplasmic environment for the ability of the incoming nucleus to support development. It should be noted that in these experiments, the nuclear cytoplasmic ratio was also an important factor in determining the development of the reconstituted embryos [2]. Similar observations were also made when monitoring the development of haploid embryos [5]. In another study, Latham and Solter [6] examined the ability of androgenones, obtained by replacing the female pronucleus of a zygote by the male pronucleus, to develop to the blastocyst stage. Androgenones generated from C57B1/6 eggs were found to be much more competent to give rise to blastocysts than were DBA/2 androgenones. However, when androgenones were constructed from (DBA/2×C57B1/6)F1, zygotes (genetic constitution of the embryos will hereafter be indicated with the female parent coming first followed by the male parent), by replacing the DBA/2 female pronucleus with a C57B1/6 pronucleus, they also developed poorly. This was not simply due to the lack of some component in DBA/2 cytoplasm, since the impaired development was also observed when C57B1/6 male pronuclei from pairs of (DBA/2×C57B1/6) F1, were transferred to an enucleated C57B1/6 egg.

The twinning incidence from 1984 to 1993 was investigated in Campinas, State of São Paulo, Brazil, and the analyzed data were combined with previous series from the same population. This study has shown that the mean annual incidences and the standard deviations for DZ, MZ and DZ plus MZ twins for the period of 1984 to 1993 are estimated respectively as 4.7 ± 0.92, 4.1 ± 1.11, and 8.8 ± 0.87 per 1,000. In the same period the mean annual incidence of triplets was 0.15 ± 0.16. It was also shown that the incidence of DZ twins is steadily decreasing since 1925, while the incidence of MZ pairs, after a period of decline is increasing since the sixties, due perhaps to the widespread use of oral contraceptives. Concerning the twinning rate as a whole, it has been shown that its declining trend has disappeared over the last few years.

The unfolding of the genetic story of Prader-Willi and Angelman syndromes provided the first recognition of human genomic imprinting. These disorders, which are clinically very distinct, are related through their genomic proximity and the inverse direction of the imprinting which affects them. Both are interesting disorders in themselves, especially in that both have distinctive behavioral patterns among their clinical features that may teach us much about normal human behavior.

Prader-Willi syndrome (PWS) is a complex multi-system condition whose major features include infantile hypotonia with decreased arousal, poor suck and failure-to-thrive; characteristic dysmorphic facial features; hypopigmentation; childhood onset of obesity due to lack of satiety; hypogonadotropic hypogonadism with genital hypoplasia and delayed and incomplete puberty; short stature for genetic background; developmental delay and usually mild mental retardation; and a characteristic behavioral disturbance with temper tantrums and obsessive-compulsive behavior. PWS occurs in about 1/15,000 people. Since its first description in 1956, it has been apparent that many of these features arise from insufficient function of the hypothalamus, and recent identification of neurosecretory growth hormone insufficiency and temperature and sleep regulation abnormalities support this. However, no visible gross or microscopic abnormalities of the hypothalamus are seen on neuropathology. The finding of a chromosome 15q 11-13 deletion in a proportion of patients with PWS by Ledbetter and colleagues in 1981 was the first window to the exciting genetic discoveries of the past decade, including recognition (initially by Butler and Palmer) that the deletion is always on the paternally-derived chromosome 15 in PWS, and the finding by Nicholls and coworkers that the vast majority of the remainder of patients had normal chromosomes but had maternal uniparental disomy (UPD). Nearly all patients with clinically typical PWS have either 15q deletion (about 75%) or maternal UPD (about 25%). This is the first human disorder that was recognized to result from uniparental disomy, and lead to many insights into imprinting.

This study included two groups of 37 children, one of twins and the other singletons at 4 years of age. All subjects had birthweights under 1500 grams and individuals in the groups were matched for birth date, gender and birthweight. Except when parental socio-economic status was taken into account, no significant differences between twins and singletons were observed on any of the results of The Stanford-Binet Intelligence Scale, nor were there any when the twins and singletons were divided into groups with birthweights < 1000 grams and 1000 to 1499 grams. When cognitive scores were analysed in relation to socio-economic status, there were significant differences in the whole population between subjects in the high and low socioeconomic status groups, with higher mean scores for the former. Comparison of the twins and singletons with parents in the lower socio-economic status group did not produce any significant differences but in the case of the upper socio-economic status group the singletons scored significantly better that the twins in Quantitative Reasoning and on the Composite Score. No significant differences were demonstrated in the clinical assessment of speech, language or behaviour. So far as general life considerations and health were concerned only one significant difference was found and this was for the number of siblings born subsequently, with more born in the singleton families. This study did not provide support for the view that singletons and twins differ significantly in the areas considered.

During the years 1964 to 1971 a nationally representative sample of MZ and DZ twins and controls was followed through the Swedish compulsory school. The main purpose was to study physical and mental growth during puberty as well as heredity-environment influences on these growth processes.

After 20 years a follow-up has been made of this sample with the purpose of investigating heredity-environment influences on life situation and self reported health at mid-life in relation to background factors collected during adolescence. 43 pairs of MZ twins, 90 pairs of DZ same sex and opposite sex twins as well 322 controls agreed to participate. A questionnaire was sent out to this group dealing with their present life situation such as family structure, economy, education and occupation. Other areas of interest were self reported health and ability to cope with their present life situation. The disadvantages found for MZ female twins at adolescence seem to persist at mid-life and ratings of school adjustment were related to coping ability as grown ups. This first report presents comparisons between twins and controls as well as males and females. To estimate heredity influences intraclass correlations for the twin pairs are calculated and for coping ability such influences seem to be quite conspicuous. Sex specific factors seem to operate regarding coping ability and satisfaction in educational choice and level. Generally, the results indicate some advantages for the males regarding self reported life situation and health. Possible reasons for such sex differences are discussed. This study has been supported by grants from the Swedish Council for Social Research.

This paper reviews four economic studies of aspects of earnings and schooling conducted by the authors using data from the Australian Twin Register. First, estimates of the economic returns to schooling made using fixed effects and selection effects regression models incorporating an instrumental variables approach to correct for measurement error in self-reported schooling levels are examined. The finding is that up to 30 per cent of the estimated return to schooling may be due to family effects and the remainder to pure educational effects. Second, comparisons are made between the economic model of Ashenfelter and Krueger (1994) and that of DeFries and Fulker (1985) and the results obtained from each are shown to be similar. Third, gender differences in returns to schooling are estimated and family effects are found to be a more important influence in the case of males. Fourth, the influence of family effects on educational attainments is considered and it is found that around one-half of educational attainment is accounted for by genetic inheritance and up to another quarter due to shared environment effects.

Maternal and paternal disomies and equivalent duplications for specific chromosome regions can readily be generated in the mouse. Most do not result in abnormality but for 10 regions distributed over 6 chromosomes developmental anomalies ranging from early embryonic lethalities to characteristic phenotypic abnormalities occur. With certain chromosome regions, maternal or paternal duplication leads to different and, in some cases, opposite anomalies so that, in total, 15 different imprinting effects can be distinguished. These observations have provided key evidence on the occurrence of imprinting in mammals.

On the basis of the established homologies between mouse and human chromosomes, it is possible to predict which segments of the human genome are subject to equivalent imprinting. In this regard it is significant that candidate imprinting effects for the two classical examples of imprinting in humans, namely the Prader-Willi and Angelman syndromes, have been found in the mouse.

Current studies are aimed at reducing the size of the imprinting regions with the objective of facilitating identification of the genes involved. Furthermore, the developmental profiles of genes already identified as being subject to imprinting are being determined.

A new approach involves the analysis of a novel mutation that causes growth retardation and cranial abnormalities and which shows the inheritance pattern of an imprinted gene, as originally predicted by Hall (Am J Hum Genet 46: 857, 1990). It is anticipated that the mutation will represent a deletion and will lie within one of the recognised imprinting regions.

The objective of this study was to determine the birthweight and gestational age associated with the lowest fetal mortality for twins and triplets. The study design was a population-based analysis of all live births and fetal deaths in the US between 1983-88. Fetal mortality was compared by categories of birthweight and gestational age, for twins and triplets versus singletons, and within each plurality by the lowest rate compared to all other rates as relative risks ± 95% Cls. The overall versus lowest fetal death rate per 1,000 conceptions for singletons was 4.3 versus 0.9 at 3700-4000 g and 40-41 weeks; for twins, 15.5 versus 3.3 at 2500-2800 g and 36-37 weeks; and for triplets, 21.0 versus 5.2 at 1900-2200 g at 34-35 weeks. Beyond these plurality-specific lowest ranges, the risk of fetal death increased, more for twins than singletons, and most for triplets. To conclude, fetal death rates can be reduced by 75-80% with attainment of birthweight and gestational age within a plurality-specific ideal range.

A high frequency of twin births has been observed in Linha São Pedro, a small settlement which belongs to the city of Cândido Godói, located 524 km Northwest from Porto Alegre, Rio Grande do Sul, Brazil, in an ethnically homogeneous population of German descent restricted to a small geographic region. From 1990 to 1994, the proportion of twin births in Linha São Pedro was 10%, significantly higher than the 1.8% rate for the state of Rio Grande do Sul as a whole. Genealogical analysis showed a high recurrence of multiple births within families, as well as a high level of inbreeding in the community. Zygosity data indicated that 9 of the 17 pairs of twins studied (53%) were dizygotic. No external environmental factors were detected that could be influencing the appearance of this characteristic. This preliminary investigation confirmed the presumed existence of a high twinning rate in the community. The high familial recurrence and the high inbreeding rate suggests the presence of genetic twinning factors. Complementary studies of twins that have yet to be evaluated and the search for additional risk factors, as well as linkage studies, should contribute to a further understanding of the biological factors related to twin births in the human species.

The comparison of MZ-DZ twins in behavioral genetics has produced what seems like irrefutable evidence for the heritability of many psychiatric disorders. But such research depends on the validity of the EEA – the “equal environments assumption” – as an underlying premise. In this paper, several empirical studies which support the EEA are critically reviewed in terms of methodology and the way data has been processed in a mathematical model called “path analysis”. It turns out that studies investigating the EEA appear to be largely inadequate in terms of technique, as well as biased in the inferences drawn. Further, the “heritability” estimate – often taken to mean the influence of trait – specific genes – is merely a statistical abstraction derived from a matrix of correlations; this estimate encompasses many buried environmental effects so that “heritability” does not correspond to any underlying DNA structure. In conclusion, many MZ-DZ pedigree studies have dubious scientific value, given the non-viable premise of the EEA, as well as the misleading operational definition of what has been called “heritability”.

The following paper is concerned with potential changes in the normal epigenetic process in a diploid individual, when a chromosome pair or segment is inherited from one parent only, instead of the expected biparental contribution. This aberrant mode of transmission arises from the high rate of gamete aneuploidy in humans. It has received the name uniparental disomy (UPD), and has emerged as an important factor in the new field of nontraditional inheritance, depicted in Table 1.

The following definitions may foster a better understanding of this discussion.

UPD is the inheritance of both copies of a chromosome [or chromosomal segment(s)] from a single parent, instead of the normal biparental transmission of the pair. In isodisomy, the two uniparental copies are identical, being derived from the same parental chromosome. In heterodisomy, the two uniparental chromosomes are different, being derived from the homologues of a pair.

Twins within pairs often have different weights at birth. A difference of 15% or greater is defined as discordance for weight and is considered to place one or both infants at risk. Temperament differences had been found in the neonatal period for full-term discordant cotwins, but not for preterm discordant cotwins, suggesting that continued gestation for discordant twins was a risk variable for early behavior. 30 pairs of fullterm and 17 pairs of preterm discordant pairs were followed at 6, 9, 12, 18, 24, and 30 months of age. Group differences were observed for the longitudinal maintenance of cotwin discordance in physical measures, with preterm cotwins becoming more like each other. In laboratory assessments, temperament differences no longer were observed between the larger and smaller cotwins. Questionnaires indicated that mothers generally did not differentiate between their larger and smaller cotwin children in temperament ratings, except for ratings of mood for the fullterm pairs. Thus, emotionality was the only temperament dimension that differentiated between the fullterm discordant twins both in the neonatal period and at later ages. In the main, it was concluded that the fullterm discordant twins overcame the adverse in-utero influences on early behavioral development.

Genetic studies have shown that both a maternally and paternally inherited copy of mouse chromosome 7 are essential for normal embryogenesis. When the parental dosage is altered, such as in maternal or paternal uniparental disomy for chromosome 7 (UPD7), the resulting embryos die. This is due to the altered dosage of imprinted genes which are normally expressed only from the paternally or maternally inherited chromosome homologue. Several genes on mouse chromosome 7 are subject to parental imprinting. Mutant phenotypes seen in UPD7 embryos and chimaeras can be explained by the altered dosage of some of these genes.

The mechanism(s) that causes genes to be expressed in a parental origin specific manner has not yet been determined but is believed to involve germline specific modifications to DNA and/or chromatin which are acted upon after fertilisation to affect the activity of imprinted genes. Two genes, H19 and Igf2, are located 90kb apart on the distal end of chromosome 7 and are imprinted reciprocally with the maternally inherited allele of HI9 and paternally inherited allele of Igf2 being expressed. We have used UPD7 embryos to identify epigenetic modifications that distinguish the two parental alleles in the H19 and Igf2 domain by comparing DNA and chromatin from normal and maternal UPD cobceptuses. Clear cut differences in DNA methylation and chromatin compaction were observed for the H19 gene with the paternal allele exhibiting promoter methylation and nuclease insensitivity. These were not found in sperm. In addition, no major differences were noted for the Igf2 gene, although subtle parental origin specific modifications were found. These studies suggest that the two genes may share a common regulatory mechanism which controls their reciprocal imprinting.

Malawi is a country in South-East Africa with a population of approximately 10 million, over 95% of whom are negro of Bantu origin. The country is divided into 24 administrative districts, each of which provides details of births which are compiled centrally at the Ministry of Health. Using data reported annually by health facilities from 1987-1990, most districts had twinning rates in the range 16 to 24 per 1000 maternities, figures consistent with those of other negro populations in Africa. Two adjoining districts (Rumphi and Mzimba) had rates which were considerably higher, almost 30 per 1000. Although ethnic origin is not recorded in the latest Malawi census, language spoken in the home, which was last recorded in 1966, can be used as a proxy. Rumphi and Mzimba are the only districts with an overwhelming majority of Tumbuka speaking population. These people, who are of both Tumbuka and Ngoni ethnic origin, therefore have an unusually high twinning rate (29.57 per 1000 maternities). The rate for the main ethnic group in Malawi, the Chewa people, was 21.21 per 1000. The district of Thyolo, with a mixed ethnic population, had by far the lowest rate (13.75 per 1000).

In most wealthy industrialized countries, socioeconomic circumstances, hygiene and medical care have improved to such an extent that perinatal complications and congenital disorders have become the major causes of infant mortality and of chronic handicap in children [1].

In the past four decades, we have made impressive advances understandig the cytogenetic and molecular basis of congenital disorders. Dozens of syndromes associated with multiple physical handicaps and mental retardation have been related to specific numerical or structural chromosome aberrations. In situ hybridization and the development of a rapidly increasing number of DNA probes enable the detection of chromosomal abnormalities with a resolution down to the level of a single gene. The discovery of tumor-associated chromosomal aberrations, microdeletions, more than a hundred oncogenes, and the cloning of tumor suppressor genes are illustrations of the importance of molecular cytogenetics.

When I started my scientific career at the end of the fifties, some 1,000 syndromes were proven or suspected to be subject to Mendelian inheritance and this number has now increased to more than 6,600 [2]. Progress in elucidating the protein defects responsible for these single gene disorders has been much slower and currently about 400 protein defects have been delineated [3]. This knowledge has been important not only for basic research on biochemical pathways and cell biology, but has also provided new perspectives for early laboratory diagnosis of index patients, carrier detection, genetic counseling and in some instances, such as phenylketonuria, for newborn screening and early treatment [4]. In those instances where a protein defect is also expressed in cultured skin fibroblasts, amniotic cells or chorionic villi, prenatal diagnosis becomes possible for couples at increased risk [5, 6].

Objective: data on the prognosis and management of multifetal pregnancies are of vital importance, particularly when the option of selective termination is considered. The present study details the obstetric management, neonatal outcome, and follow-up data of 65 quadruplet pregnancies in France.

Methods: to conduct the study, a questionnaire was sent to families registered with the National Association Helping Parents of Multiple Births (Association National d'Entraide des Parents de Naissance Multiples, A.N.E.P.N.M.).

Results: of 116 questionnaires sent to families of quadruplets born between 1972 and 1988, 65 were received. Of these pregnancies, 58 were obtained with ovulation induction agents, 2 with IVF (in vitro fertilization) and GIFT (gamete intrafallopian transfer) and 5 were spontaneous. Diagnosis was made prior to 13 weeks gestation in 87.2% of cases. Most mothers were hospitalized prior to delivery – mean duration of 47 days. The mean gestational age at delivery was 31.2 ± 3 weeks with a prematurity rate of 97%. Cesarean sections were performed in 51 cases and vaginal deliveries in 14. Neonatal and perinatal mortality rates were 68 and 104 per 1000, respectively. Birthweights of quadruplets ranged from 760 to 2455g with a mean of 1615 g.

Conclusion: management of quadruplet pregnancies in France consists of early diagnosis, echographical and clinical monitoring, early reduction of maternal activity and cesarean deliveries. Our management of such pregnancies is of high quality as reflected by our obstetrical results. Lack of adequate management, as perceived by families of quadruplets, exists at two levels: a psychological (lack of psychological support) and a financial (lack of specific help).

This study falls in the areas of both differential psychology and twin psychology. Using the EFT and the WCST (computerized version), we examined 11 MZFF pairs between 18 and 35 years of age. The aim was to establish the genetic and/or environmental determination of global-analytical cognitive style as well as some characteristics of conceptualization linked to field dependence. The research strategy consisted of introducing three other groups of the same size to control the weight of environmental factors different from those determined by subject selection. The results seem to support the hypothesis of genetic determination of field dependence of the MZFFs, probably linked to the XX chromosome combination. The “couple effect” and the attitude of parents and others toward two identical female subjects may contribute to full expression of the genome. The characteristics of conceptualization revealed by the WCST show that MZFFs persevere in errors typical of a global approach to experience.

Population studies on human twinning are scarce in Argentina. In order to analyze frequencies and certain maternal and neonatal variables related to twin births, we studied a series of 69.678 consecutive newborns with 500 g of weight and over, which occurred at a public hospital in the province Buenos Aires, during 14 years (1982-1995). The frequency of twin births (10 per 1000 deliveries) and sex ratio were similar to other studies reported in Caucasian population. Maternal age and order of gravity/parity were positively correlated with twinning rates, more markedly so in dissimilar sex-pairs. Stillbirths and neonatal deaths were more frequent in twins than in singletons, but less frequent when comparing groups of same weight. Congenital malformations were not found to be significantly more frequent in twins than in the total newborn population. However, their occurrence, predominantly in like-sexed pairs and the concordance for defect type in doubly affected same-sex pairs, suggests that monozygotic twinning carries an increased risk for malformation.

Pediatric Gastroenterology was born as specialism within Pediatrics during the 1960s, and its younger sister, Hepatology, gradually acquired respect as an autonomous field early in the 1970s, with the formation of the Pediatric group for Gastroenterology, and more recently in 1992 with the creation of the Italian Society for Pediatric Gastroenterology and Hepatology in the Italian Society of Pediatrics. My aim in this paper is to review the most significant developments that have taken place in Pediatric Hepatology over the past decade, and to indicate how the field is likely to develop in the future. I will make particular reference here to HBV infection, cholelithiasis, extrahepatic biliary atresia, and liver transplants.

In Italy, this remains one of the most common causes of chronic hepatitis in children. (HCV infection in children without an underlying illness is still uncommon). Since the 1960s, we have gained an understanding of the risk factors, pathogenesis and natural history of infection, and an awareness of the strong tendency for the condition to become chronic in children. Moreover, with the increase in knowledge of the biology of the virus, an efficacious programme of preventive medicine has been implemented, which 3 years ago culminated in obligatory vaccination for newborns and 12-year-old children. These measures have resulted in a change in the epidemiology of the infection, which is now found above all in foreign children residing in Italy, who have been usually adopted.

Over the last 10 years, the phenomenon of international adoption represents a new socio-sanitary reality in the industrialized countries. A number of important studies report that, more than 50 percent of foreign children adopted present serious medical condition (irrespective of the area of the world from which they come, be it Asia, Africa, South America, or Eastern Europe). If routine screening is not carried out, these disorders go undetected by medical tests performed in the children's countries of origin, as well as by medical examinations carried out in their adoptive countries [4]. The most frequent diseases are infections, and amongst these HBV infection, besides TBC and CMV infection, making those children in whom such infections go undetected veritable spring of disease [3].